Mechanism of insulin secretion by midaglizole

Midaglizole was introduced as a hypoglycemic agent, but its Insulin releasing mechanism remains unknown. In the present study, the effect of midaglizole upon the B cell function of the pancreas was investigated, using an in situ local circulation of the canine pancreas. The graded doses of midaglizole (0.2, 1.0 and 2.0 mg/kg) revealed a dose-related response of plasma Insulin. The administration of yohimbine, a classical alpha 2-antagonist (1.11 mg/kg) revealed a similar increase in plasma Insulin to that with midaglizole of equimolar amount. During the clonidine infusion midaglizole did not elicit any significant rise in plasma Insulin, whereas yohimbine increased plasma Insulin significantly. During glucagon infusion plasma Insulin increased following midaglizole infusion but not by yohimbine. The simultaneous administration of diazoxide (K-channel opener) suppressed the midaglizole-induced Insulin secretion. These results obtained in the present experiments revealed a different mechanism of Insulin releasing action of midaglizole from that of yohimbine. Furthermore, the finding with diazoxide administration suggests that midaglizole stimulates Insulin release through an interaction of K(+)-channel of the pancreatic B-cell.